From: . Health_and_HealingSSRI-Research
Date: Sun, 27 Nov 2005 20:06:23 -0500
Subject: [SSRI-Research] Archive: Lilly knew about
Prozac-induced
suicidality and violence (even before Prozac was approved
for
marketing in the United States) and that this was withheld
from the
public.
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Below is the time-line presented to the jury in the Forsyth
v. Eli
Lilly Trial. It was presented during closing arguments by
the
plaintiffs. It lists Lilly's internal documents. The
plaintiffs allege
that it shows that Lilly knew about Prozac-induced
suicidality and
violence (even before Prozac was approved for marketing in
the United
States) and that this was withheld from the public.
htt
p://ethics.ucsd.edu/seminars/2004/february.htm
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1 Aug. 1978 - Team Meeting Minutes - "There have been
a fairly
large number of reports of adverse reactions . . . Another
depressed
patient developed psychosis . . . Akathisia and restlessness
were
reported in some patients." Exhibit 30 (2nd page, end
of 2nd paragraph)
2 May 1984 - BGA Comments - "During the treatment with
the
preparation (Prozac) 16 suicide attempts were made, 2 of
these with
success. As patients with a risk of suicide were excluded
from the
studies, it is probable that this high proportion can be
attributed to
an action of the preparation (Prozac) . . ." Exhibit 42
(page 3, 6th
paragraph)
3 Jan. 1985 - Lilly receives reasons why the BGA will
reject
Lilly registration, one of which was because of
"SUICIDAL RISK." With
instructions for "IMMEDIATE FOLLOW-UP ON ALL KEY
OPINION LEADERS ON
THE BGA COMMISSION FOR SELECTED VISITATION NEXT WEEK."
Exhibit 53
4 March 29, 1985 - "Benefit/Risk Considerations"
- "The
incidence rate (suicide) under fluoxetine (Prozac) therefore
purely
mathematically is 5.6 times higher than under the other
active
medication imipramine." . . . "The benefits vs.
risks considerations
for fluoxetine (Prozac) currently does not fall clearly in
favor of
the benefits. Therefore, it is of the greatest importance
that it be
determined whether there is a particular subgroup of
patients who
respond better to fluoxetine (Prozac) than to imipramine, so
that the
higher incidence of suicide attempts may be tolerable."
Exhibit 58
(pages 18 & 22)
5 June 1986 - Draft of Proposed PRECAUTIONS and ADVERSE
REACTIONS Sections of the Prozac Package Insert -
"Mania and psychosis
may be precipitated in susceptible patients by
antidepressant
therapy." Exhibit 5 (1st page) (never included in
actual inserts)
6 Aug. 1989 - Additional Feedback Regarding the Fluoxetine
(Prozac) Review by the Commission A (Germany) - "3. The
counterindication because of acute suicidality should become
a warning
whereby the physicians should be advised that in the absence
of
sedation, the risk of higher suicidality should be taken
into
account." Exhibit 88
7 Nov. 17, 1989 - Letter to sales representatives on
article
about Prozac-induced akathisia authored by Dr. Lipinski and
others.
"In the article the authors voice their suspicion that
'the triad of
symptoms' (anxiety, nervousness, and insomnia) reflects the
syndrome
of akathisia, 'which, in their view is apparently related to
fluoxetine (Prozac) therapy." But the sales people are
warned: "Use of
this information in product discussions may violate federal
law."
Exhibit 91 (1st page, 2nd paragraph and 2nd page, last
sentence)
8 Jan. 1990 - PROZAC and SELF-DIRECTED VIOLENCE - "We
have just
received a pre-print of an article (not a letter to ed.)
Which we
understand is to appear in the February 1990 AMERICAN
JOURNAL OF
PSYCHIATRY suggesting that Prozac can induce severe,
intense,
obsessional suicidal ideation." . . ." Exhibit 94
9 Jan. 30, 1990 - Letter to sales representatives giving
the
sales people a "heads-up" on the forthcoming
Teicher article regarding
Prozac and Suicide and instructing them as follows:
"Because these
issues (suicide) are not part of our current marketing plan,
you
should not initiate discussions on these articles. ...
"Again, because
these issues are not part of our current marketing plan,
discussions
should not be initiated by you." Exhibit 15 (bottom of
second page)
10 Feb 1990 - Teicher article published "Emergence of
Intense
Suicidal Preoccupation During Fluoxetine (PROZAC)
Treatment" - "The
purpose of this report is to suggest the surprising
possibility that
fluoxetine (Prozac) may induce suicidal ideation in some
patients." .
. . "In our experience, this side effect has occurred
in 3.5% of
patients receiving fluoxetine (Prozac) . . ." Exhibit
95
11 February 7, 1990 - Leigh Thompson Memo - "Anything
that
happens in the UK (England) can threaten this drug (Prozac)
in the US
and worldwide. We are now expending enormous efforts fending
off
attacks because of (1) relationship to murder and (2)
inducing
suicidal ideation." Exhibit 97
12 February 7, 1990 - Leigh Thompson Memo - "I am
concerned
about reports I get re UK attitude toward Prozac safety.
Leber (FDA)
suggested a few minute ago we using CSM database to compare
Prozac
aggression and suicidal ideation with other antidepressants
in UK.
Although he is a fan of Prozac and believes a lot of this is
garbage,
he is clearly a political creature and will have to respond
to
pressures. I hope Patrick realizes that Lilly can go down
the tubes if
we lose Prozac and just one event in the UK can cost us
that." Exhibit 98
13 June 1990 - Letter to Lilly by concerned doctor -
"I am
writing to inform Eli Lilly Company that a disturbing number
of
suicides or suicide attempts associated with Prozac has come
to my
attention over the last several months." I am concerned
that the
association with Prozac may be more than coincidental."
. . . "There
appears to be growing concern that Prozac may somehow
trigger a
suicidal preoccupation in a small subset of patients and
that their
families should be warned of this potential risk. It is
certainly
possible that some of the cases reported are
"coincidence" in that the
depressed person may have attempted suicide independently of
Prozac.
However, some of these cases appear to be in patients taking
Prozac
for reasons other than depression." Exhibit 102 (2nd
page)
14 July 18, 1990 - Memo regarding call from Paul Leber at
the
FDA. "Paul Leber called yesterday; I contacted him at
6:15 am this
morning and half-hour conversation, very, very pleasant . .
." "The
call was about suicide." . . . "He asked that we
FAX nothing to him
unless he has agreed before hand." "Paul (Leber)
is taking a position
in talking with outside folks today that Lilly and FDA
working
together on the suicide issue and following closely the
postmarketing
events, but that there are no denominators and the best that
can be
done is to put a 'cap' on the number of events."
Exhibit 104 (top of
1st page and bottom of 2nd page)
15 August 3, 1990 - Letter to sales representatives
regarding
reports of suicidal ideation/behavior possibly associated
with PROZAC
therapy. "This information is not intended to replace
our current
promotional strategy but is being provided to enable you to
respond to
physicians when appropriate. You should not initiate
discussion on
these issues nor use this letter in detailing. However, if
asked to
comment on these issues by a health care professional, you
should: 1.
Reassure the health care professional that no casual
relationship has
been established between suicidal ideation and PROZAC
therapy."
Exhibit 17 (bottom of 1st page and top of 2nd page)
16 August 31, 1990 - "Dear Doctor" letter
assuring them that
there is no "causal relationship between Prozac and
suicidality
(ideation or acts)." Exhibit 22
17 September 12, 1990 - Lilly memo between Max Talbot and
Leigh
Thompson- Talbot says "One possible strategy if FDA
presses for an
additional labeling change vis-a-vis suicide is a class-wide
(i.e. ALL
antidepressants) cautionary note; however we should take
this position
only as a last resort." Thompson replies: "that
report MUST move
swiftly through approval and to Dr. Leber's (FDA) hands - -
he is our
defender." Exhibit 109
18 September 14, 1990 - Lilly memo between John
Heiligenstein
(Lilly) and Leigh Thompson - Heiligenstein says: "We
feel caution
should be exercised in a statement that "suicidality
and hostile acts
in patients taking Prozac reflect the patient's disorder and
not a
causal relationship to Prozac - - - - Postmarketing reports
are
increasingly fuzzy and we have assigned 'Yes, reasonably
related' on
several reports.". . . "You may want to note that
trials were not
intended to address issue of suicidality." Exhibit 110
19 September 25, 1990 - Minutes of Lilly Meeting with FDA -
discuss doing an in-hospital rechallenge of patients who met
predefined criteria for suicidal acts and ideation and
agrees to
"analyze international data relating to suicide."
Exhibit 112
20 October 2, 1990 - Memo to Lilly employee Leigh Thompson
to
Lilly employee Robert Zerbe regarding an upcoming Prozac
symposium in
which the issue of suicidality is discussed. "Then the
question is
what to do with the 'big' numbers on suicidality. If the
report
numbers are shown next to those for nausea, they seem
small." Exhibit
113 (2nd page.)
21 November 7, 1990 - Leigh Thompson memo - "I'd
suggest that
priorities are: (1) protect Prozac" . . . Exhibit 116
22 November 13, 1990 - Memo from Claude Bouchy (Lilly
Germany)
to Leigh Thompson Re: Adverse Drug Event Reporting - Suicide
Fluoxetine - In response to Lilly's request that he (Bouchy)
change
the event "suicidal ideation" to
"depression," Bouchy writes: "Hans
(another Lilly employee in Germany) has medical problems
with these
directions and I have great concerns about it. I do not
think I could
explain to the BGA, a judge, to a reporter or even to my
family why we
would do this especially on the sensitive issue of suicide
and
suicidal ideation." Exhibit 117
23 November 14, 1990 - Second memo from Claude Bouchy
(Lilly
Germany) to Leigh Thompson Re: Adverse Drug Event Reporting
- Suicide
Fluoxetine in which he states: "I personally wonder
whether we are
really helping the credibility of an excellent ADE system by
calling
overdose what a physician reports as suicide attempt and by
calling
depression what a physician is reporting as suicide
ideation." Exhibit 118
24 April 15, 1991 - Memo to Leigh Thompson called
"Upcoming TV
appearance" Section I. "MESSAGE GOALS - Whatever
questions you are
asked or direction the interview take, the three points we
want to
establish are: 2. 'It's in the disease, not the drug.';
Section III
'If pressed, or as a postscript to the above, then make the
point that
absolutely no evidence indicates that PROZAC as a cause of
such
behavior (violence and suicide).', and 'Prozac defense . . .
There is
simply no medical or scientific merit to the argument."
Exhibit 123
25 April 23, 1991 - Leigh Thompson Memo re 20/20 Show in
which
he admits that on the issue of suicidality "I did NOT
share the
European data AT ALL." and "She attacked on us
hiding data by dividing
up reports by many COSTART terms. She had numbers for
suicide,
overdose, intentional overdose, unintentional overdose and
said they
came to 1200 (or 1400) total suicides - - so we went around
on OD not
necessarily being suicide and COSTART, etc." Exhibit
124 (bottom of
1st page and 4th paragraph of 2nd page)
26 May 15, 1991 - FDA Meeting to Discuss Fluoxetine
Rechallenge
Protocol - "we agreed to have the rechallenge protocol
ready to go by
September 1, 1991 Exhibit 125
27 August 1991 - Dr. David Healy's Article
"Antidepressant
Induced Suicidal Ideation" - "These two cases
suggest that the
emergence of suicidal ideation on antidepressants cannot
always be
attributed to a lifting of psychomotor retardation but
rather that the
ideas may in some instances be produced by
antidepressants." Exhibit 126
28 October 29, 1991 - Lilly prepared draft for Dr. Beasley
entitled "Suggested Reply Points to Oswald, Healy &
Creaney" in which
he acknowledges that item 3 of the HAMD is an insensitive
measure of
suicidality and states:"There was no specific rating
scale for
akathisia included in the trial designs for the studies
reported, so
the only source of data would be adverse event reports.
Akathisia is a
subjective phenomenon and hence would rely on patients
volunteering
information." Exhibit 130 (2nd page)
29 December 1991 - Dr. Rothschild's Article
"Re-exposure to
Fluoxetine After Serious Suicide Attempts by Three Patients:
The Role
of Akathisia" - "This is the first report, to our
knowledge, of
patients restarted on fluoxetine (Prozac) after a previous
suicide
attempt during fluoxetine treatment." . . ."When
re-exposed to
fluoxetine, the patients again developed akathisia and
suicidal
ideation. The suicidal feelings abated when the akathisia
was treated
by the discontinuation of the fluoxetine (Prozac) or the
addition of
propranolol." Exhibit 131 (Cross-examination)
30 January 23, 1992 - Lilly memo regarding upcoming meeting
with Taiwanese doctors (Drs. Lu and Ko) to discuss the
report on their
study results entitled "suicidal attempts and
fluoxetine (Prozac)
treatment." Exhibit 133
31 April 8, 1992 - Weinstein (Lilly employee) Report -
"Mission
Accomplished. Professor Lu will not present or publish his
fluoxetine
(Prozac) vs. maprotiline suicidality data." Exhibit 144
32 March 3, 1993 - Forsyth's deaths
33 1994 - Dr. David Healy's Article "The Fluoxetine
and Suicide
Controversy" - Dr. Healy concludes: "In the
opinion of this author,
the volume of case reports and other studies is sufficient
to
demonstrate that antidepressants and antipsychotics may
induce
suicidal ideation in certain individuals under certain
conditions."
Exhibit 153
34 1995 - Dr. Jick's Study "Antidepressants and
Suicide" - "The
results indicate that only fluoxetine (Prozac) has a rate
that seems
to be substantially higher than that of the other
antidepressants."
Exhibit 155
35 June 1998 - Dr. Roger Lane's article "SSRI-Induced
Extrapyramidal Side-Effects and Akathisia; Implications for
Treatment"
appears in the Journal of Psychopharmacology.
"SSRI-induced akathisia
is a relatively rare but is frequently unrecognized when it
does
occur." . . . "The precise definition of akathisia
is a matter of
controversy, as is the relative importance of the objective
and
subjective aspects of the disorder. Is akathisia a movement
disorder
or an intense and uncomfortable mental state . . ."
"It may be less of
a question of patients experiencing fluoxetine
(Prozac)-induced
suicidal ideation, than patients feeling that 'death is a
welcome
result' when the acutely discomforting symptoms of akathisia
are
experienced on top of already distressing disorders."
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